Clinical Trial: Sorafenib Tosylate in Treating Patients With Desmoid Tumors or Aggressive Fibromatosis

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase III, Double Blind, Randomized, Placebo-Controlled Trial of Sorafenib in Desmoid Tumors or Aggressive Fibromatosis (DT/DF)

Brief Summary: This randomized phase III trial compares the effects, good and/or bad, of sorafenib tosylate in treating patients with desmoid tumors or aggressive fibromatosis. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the proteins needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To compare the progression-free survival (PFS) rates of patients with desmoid tumors (DT)/deep fibromatosis (DF) who receive either sorafenib (sorafenib tosylate) or placebo using a double-blinded randomized phase III study.

SECONDARY OBJECTIVES:

I. To assess toxicity. II. To assess time to surgical intervention. III. To assess tumor response rates and survival.

TERTIARY OBJECTIVES:

I. To evaluate changes in magnetic resonance imaging (MRI) Tesla (T)2 to predict (or correlate) with a biological effect such as tumor growth (by Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1), and pain palliation. (Correlative companion study) II. The mechanism of action of sorafenib in DT/DF remains unknown. In patients consenting to undergo the paired tumor biopsies (A091105-ST1), treatment induced changes will be quantified by histology, gene expression profiling, proteomic changes and selected interrogation of key pathways by western blot and reverse transcription-polymerase chain reaction (RT-PCR). (Correlative companion study) III. To collect archival tissue, baseline (tumor, blood) and day 8 (tumor, blood) specimens for basic science research (A091105-ST1). (Correlative companion study) IV. To assess patient-reported adverse events and quality of life (QOL) as measured by the Patient-Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) and the single-item overall Linear Analogue Self-Assessment (LASA) (A091105-HO1). (Correlative companion study) V. To assess pain palliation measured by the "worst pain" item of the Brief Pain Inventory Short Form (A091105-HO1). (Correlative companion study)

Data following cross over will be analyzed and summarized separately from the data from the main course of treatment for these patients. Intention to treat principles will be used.



Original Primary Outcome: PFS [ Time Frame: Time from randomization to the first occurrence of progression or death due to any cause, assessed up to 3 years ]

Data following cross over will be analyzed and summarized separately from the data from the main course of treatment for these patients. Intention to treat principles will be used.


Current Secondary Outcome:

  • Best objective status between the two treatment arms according to Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 3 years ]
    Compared between the two treatment arms and using the Cochran-Mantel-Haenszel test.
  • Duration of response [ Time Frame: Time between first tumor response and progression, assessed up to 3 years ]
    Kaplan Meier methodology will be used to estimate the distribution of duration of response and the log-rank test will be used to test for a difference in duration of response between the two arms.
  • Incidence of adverse events, using the Patient Reported Outcomes-Common Terminology Criteria in Adverse Events version 4.0 [ Time Frame: Up to 3 years ]
    Frequency tables, summary statistics, and categorical analysis will be used to compare the distributions of toxicity for patients treated with sorafenib tosylate vs placebo. Data for patients who have crossed over or having received surgical or radiotherapy intervention will be summarized independently from their primary course of study treatment.
  • Overall survival [ Time Frame: Time between the date of randomization to until death, assessed up to 3 years ]
    Kaplan-Meier methodology and log rank tests will be used to compare overall survival between the groups at various time points (eg, 1 year rate, 2 year rate, etc) and 95% confidence intervals will be calculated for these estimates. Data following crossover will be analyzed and summarized separately from the main course of treatment for these patients.
  • Time to surgical intervention during treatment [ Time Frame: Time between randomization to the patient undergoing therapeutic surgical resection for this disease, assessed up to 3 years ]
    A log rank test will be used to compare the distributions of time to surgical intervention between the two arms using a 2-sided test and alpha=0.05 level of significance. Kaplan-Meier methodology will be used to estimate various time points and 95% confidence intervals will be calculated for these estimates. Surgery will be classified by outcome (eg, complete-macroscopic, complete-microscopic, or partial), type, location (eg, limb), thereafter analyzed by categorical analysis and descriptive statistics. Non-parametric methods will be used, as appropriate.


Original Secondary Outcome:

  • Incidence of adverse events, using the PRO-CTCAE v4.0 [ Time Frame: Up to 3 years ]
    Frequency tables, summary statistics, and categorical analysis will be used to compare the distributions of toxicity for patients treated with sorafenib tosylate vs placebo. Data for patients who have crossed over or having received surgical or radiotherapy intervention will be summarized independently from their primary course of study treatment.
  • Time to surgical intervention during treatment [ Time Frame: Time between randomization to the patient undergoing therapeutic surgical resection for this disease, assessed up to 3 years ]
    A log rank test will be used to compare the distributions of time to surgical intervention between the two arms using a 2-sided test and alpha=0.05 level of significance. Kaplan-Meier methodology will be used to estimate various time points and 95% confidence intervals will be calculated for these estimates. Surgery will be classified by outcome (eg, complete-macroscopic, complete-microscopic, or partial), type, location (eg, limb), thereafter analyzed by categorical analysis and descriptive statistics. Non-parametric methods will be used, as appropriate.
  • Overall survival (OS) [ Time Frame: Time between the date of randomization to until death, assessed up to 3 years ]
    Kaplan-Meier methodology and log rank tests will be used to compare OS between the groups at various time points (eg, 1 year rate, 2 year rate, etc) and 95% confidence intervals will be calculated for these estimates. Data following crossover will be analyzed and summarized separately from the main course of treatment for these patients.
  • Best objective status between the two treatment arms according to RECIST v1.1 [ Time Frame: Up to 3 years ]
    Compared between the two treatment arms and using the Cochran-Mantel-Haenszel test.
  • Duration of response [ Time Frame: Time between first tumor response and progression, assessed up to 3 years ]
    Kaplan Meier methodology will be used to estimate the distribution of duration of response and the log-rank test will be used to test for a difference in duration of response between the two arms.


Information By: National Cancer Institute (NCI)

Dates:
Date Received: February 17, 2014
Date Started: March 2014
Date Completion:
Last Updated: May 12, 2017
Last Verified: May 2017